Biomedical subjects

A A Boldyrev

Publications and source records attributed to A A Boldyrev.

At least 19 recordsLinked to original sources

PubMed2005

Homocysteinic acid causes oxidative stress in lymphocytes by potentiating toxic effect of NMDA.

Short-term incubation of lymphocytes with homocysteine or its oxidation product homocysteinic acid increased the formation of reactive oxygen species and cell necrosis (in case of homocysteinic acid). Effective concentration of homocysteine and homocysteinic acid (500 microM) significantly surpassed the level observed during hyperhomocysteinemia. The addition of homocysteinic acid in a nontoxic concentration of 100 microM potentiated the toxic effect of NMDA and led to massive cell death. During hyperhomocysteinemia the amount of these metabolites in the blood was much higher than in the brain. Oxidative stress produced by these substances can result from activation of NMDA glutamate receptors that were recently detected on lymphocytes.

Animals↗

PubMed2004

[SAM (Senescence Accelerated Mice) as a model for studying the ageing and age associated diseases (from II Int. Meeting "Modern Problems of Gerontology and SAM as an aging model", July 21-23, 2003, Sapporo, Japan)].

Among several models of aging and age-associated diseases SAM is one of the most appropriate one, which provides studying the mechanisms of aging being not interfered with adaptation processes. SAM model was created by T. Takeda et al. around 80th of the previous century by brother/sister mating. The line is characterized by sufficiently shortened life-span (till 1 year) and several aging features like osteoporosis (SAMP6), memory and learning deficit (SAMP10), neurodegenerating diseases (SAMP3). All these defects are based on the disordering of oxidative metabolism, disturbing to some extent their metabolism. In short review possible reasons of such deviations in SAM metabolism are discussed focused during II International Meeting on modern problems of gerontology being hold on Sapporo between July 21-23, 2003.

Aging↗

PubMed2003

Protective effect of carnosine on Cu,Zn-superoxide dismutase during impaired oxidative metabolism in the brain in vivo.

Natural hydrophilic antioxidant carnosine protects cerebral cytosolic Cu,Zn-superoxide dismutase (SOD) under conditions of oxidative stress in various in vivo models: short-term hypobaric hypoxia in rats and accumulation of age-related changes in senescence-accelerated mice (SAMP). Administration of carnosine preventing Cu,Zn-SOD inactivation reduced mortality in rats and prolonged average life span in SAMP-mice.

Aging, Premature↗

PubMed2003

Laser modification of the blood in vitro and in vivo in patients with Parkinson's disease.

The effect of He-Ne laser radiation on activity of MAO B, Cu/Zn-SOD, Mn-SOD, and catalase in blood cells from patients with Parkinson's disease was studied in vivo and in vitro. The effects of intravenous in vivo irradiation (intravenous laser therapy) were more pronounced than those observed in similar in vitro experiments. It is concluded that generalized effect of laser therapy involves interaction between blood cells.

Blood↗

PubMed2003

Effect of NMDA on production of reactive oxygen species by human lymphocytes.

Low concentrations (<20 microM) of N-methyl-D-aspartate (NMDA), an agonist of specific receptors of brain glutamatergic systems, promote the formation of reactive oxygen species (ROS) both in the whole blood and in lymphocyte fraction. Further increase in NMDA concentrations led to progressive increase in ROS content in the whole blood, but to its decrease in lymphocyte suspension. The activating effect of NMDA is abolished by antioxidant N-acetylcysteine (5 mM) and NMDA-type glutamate receptor antagonist MK-801 (5 microM). Phorbol myristate acetate (PMA, 1 microM) also increased ROS content in the examined structures. This effect was antagonized by N-acetylcysteine, but not MK-801.

Humans↗

PubMed2002

Effect of carnosine on Drosophila melanogaster lifespan.

A positive dose-dependent effect of carnosine (beta-alanyl-L-histidine) on the lifespan of male Drosophila melanogaster flies was shown. The mean lifespan of male flies receiving 200 mg/liter carnosine approached that of females. At the same time carnosine had no effect on the lifespan of female flies. This positive effect of carnosine probably reflects its protective action against age-related accumulation of free radicals and did not depend on carnosine metabolism in the body. Addition of 200 mg/liter histidine and beta-alanine (separately or in combination) had no effect on the mean lifespan of flies.

Animals↗

PubMed2002

Activation of glutamate receptors inhibits Na/K-ATPase of cerebellum granule cells.

Na/K-ATPase prepared from cerebellum granule cells of 10-12-day-old mice is inhibited by glutamate and its agonists, NMDA (ligand for ionotropic receptors) and ACPD (ligand for metabotropic receptors). The inhibition is specific and prevented by subsequent antagonists (MK-801 for ionotropic NMDA-receptors and MCPG for metabotropic receptors). The inhibiting effect of NMDA is significantly reversed by cysteine and that of ACPD by chelerythrine or indolyl maleimide. It is concluded that ionotropic receptors inhibit Na/K-ATPase because of intracellular production of reactive oxygen species, and metabotropic receptors mediate their effect via protein kinase C.

Alkaloids↗

PubMed2001

Na/K-ATPase as an oligomeric ensemble.

Differences in the kinetic behavior and properties of monomeric and oligomeric forms of membrane-bound Na/K-ATPase are analyzed. It is concluded that enzyme molecules within oligomeric complexes are affected by extrinsic signals that result in change of enzyme activity, whereas the individual (protomeric) state is insensitive to these signals. Some of the major factors of such regulation are microviscosity of the lipid environment, reactive oxygen species, and intracellular protein kinases.

Adenosine Triphosphate↗

PubMed2001

Antioxidant systems in tissues of senescence accelerated mice.

Significant decrease in the level of lipid antioxidants (measured from the kinetics of the induced chemiluminescence in brain homogenate) and of the hydrophilic antioxidant carnosine as well was observed in the brain of 14-16-month-old mice of SAMP1 line, which is characterized by accelerated accumulation of senile features, in comparison with the control line SAMR1. In the brain of SAMP1 animals the activity of cytosolic Cu/Zn-containing superoxide dismutase (SOD) was reduced, while the activity of membrane-bound Mn-SOD was at an extremely low level. The activity of glutathione-dependent enzymes (glutathione peroxidase, glutathione reductase, and glutathione transferase) did not differ in the brain of SAMP1 and SAMR1 animals, and catalase activity was similarly low in both cases. At the same time, excess concentration of excitotoxic compounds, significantly exceeding that for the control line, was determined in the brain and blood of SAMP1 animals. The activity of glutathione enzymes in liver and heart as well as the activity of cytosolic Cu/Zn-SOD in liver did not differ in the two studied lines, while the activity of erythrocyte glutathione peroxidase was slightly increased, and the activity of liver catalase and erythrocyte Cu/Zn-SOD was significantly decreased for SAMP1 compared with SAMR1. The results demonstrate that the accelerated ageing of SAMP1 animals is connected to a significant extent with the decreased efficiency of the systems utilizing reactive oxygen species (ROS) in tissues.

Aging↗

PubMed2001

Peculiarities of carnosine metabolism in a patient with pronounced homocarnosinemia.

The article describes a case of homocarnosinemia with increased liquor and plasma content of homocarnosine, increased urinary excretion of homocarnosine, and low activity of serum carnosinase. These metabolic disturbances were accompanied by moderate neurological disorders. Changes in carnosine metabolism in family members were less pronounced and not accompanied by neuropathological symptoms.

Adolescent↗

PubMed2000

Does ethanol metabolism affect erythrocyte hemolysis?

The effects of ethanol and acetaldehyde on the hemolytic stability of rabbit erythrocytes have been compared. Incubation of normal erythrocytes with ethanol facilitated both acidic and oxidative hemolysis and increased the percentages of cells that were hemolyzed at maximal rate. Acetaldehyde exerted a similar destabilizing effect on erythrocytes only in the case of oxidative hemolysis. The destabilizing effect of ethanol was observed in catalase-inactivated erythrocytes under acidic, but not oxidative, hemolysis conditions. It is concluded that the destabilizing effect of unmetabolized ethanol occurs under conditions of acidic hemolysis, whereas the destabilizing effect of the oxidation of ethanol to acetaldehyde takes place only under the conditions of oxidative hemolysis.

Acetaldehyde↗

PubMed2000

Effects of carnosine and related compounds on the stability and morphology of erythrocytes from alcoholics.

The effects of carnosine and related compounds on erythrocytes from alcoholics were studied. In their presence, erythrocytes showed an increased ability to resist haemolysis and showed a more normal morphology, with carnosine and N-acetyl-carnosine being the most effective compounds. These beneficial properties of the dipeptides do not appear to be directly related to their antioxidant or buffering properties.

Adult↗

PubMed2000

Effect of ethanol on the hemolytic stability of erythrocytes.

The stability of rabbit erythrocytes to hemolysis induced by different compounds in the presence or absence of ethanol or acetaldehyde has been analyzed. Ethanol slightly reduced erythrocyte stability against acidic hemolysis only after long-term preincubation, but the effect of ethanol on stability to oxidative hemolysis manifested itself immediately after its addition to the cells. Ethanol decreased both stability of cells to oxidative damage and dispersion of the hemolytic curve. Comparison of the effects of ethanol and acetaldehyde showed that the destabilizing effect of ethanol might be caused by either its direct action or the effect of its metabolites formed during preincubation of ethanol with erythrocytes. Possible mechanisms of ethanol and acetaldehyde effects on erythrocyte stability are discussed.

Acetaldehyde↗

PubMed2000

Problems and perspectives in studying the biological role of carnosine.

In describing carnosine among the constituents of muscle tissue in 1900, V. Gulevitsch opened the question of its real biological role. Investigation of carnosine-related phenomena occurred simultaneously with the study of its metabolic transformation within the cell. It has now been demonstrated that carnosine has the ability to protect cells against oxidative stress as well as to increase their resistance toward functional exhaustion and accumulation of senile features. Mechanisms of such protection are explained in terms of proton buffering, heavy metal chelating, as well as free radical and active sugar molecule scavenging, preventing modification of biomacromolecules and keeping their native functional activity under oxidative stress. Several carnosine derivatives are characterized by different rates of splitting by tissue carnosinase and by different biological efficiencies, thus the biological significance of enzymatic modification of carnosine during its tissue metabolism may be increased resistance of cells operating under unfavorable conditions.

Animals↗

PubMed2000

Discrimination between apoptosis and necrosis of neurons under oxidative stress.

Flow cytometric studies of rat cerebellum neurons are described under conditions inducing cell death. Using a double labeling technique, discrimination between apoptotic and necrotic cell transformations is demonstrated. Histidine containing neuropeptides were found to regulate cell stability, taking part in selection of the preferable way of neuronal death under oxidative stress.

Animals↗

PubMed2000

Na+,K+-ATPase: 40 years of investigations.

Nobel Prize of 1997 in chemistry was awarded to three scientists fruitfully working in bioenergetics. J. Walker and P. Boyer were awarded the Prize for studies of structure and mechanism of functioning of the H+-transporting (mitochondrial) adenosine triphosphatase. The decision of the Nobel Committee was not unexpected, since these works were very impressive. Special attention was drawn to the fact that the investigations of Walker, the recognized specialist in protein structure, made possible the experimental confirmation of regularities in the mitochondrial ATPase functioning discovered by P. Boyer. The third member of this triumph of bioenergetics is Jens-Christian Skou who described the Na+,K+-activated ATPase in 1957 and then characterized the enzyme properties in detail. Forty years of his scientific biography were devoted to this enzyme. Along with accumulation of scientific knowledge, that constituted the fundamental contribution to bioenergetics (J.Skou is rightfully considered as one of founders of this branch in the present-day biology), the world-wide known school of scientists was established, and starting from 1974, members of this school organize regular conferences on this enzyme.

Biochemistry↗

PubMed2000

[Antioxidant therapy in ischemic stroke].

The paper presents the results of investigation of emoxipin, an antioxidant synthetic drug, for treatment of patients with ischemic disorders of cerebral circulation. The drug produced a beneficial clinical effect in patients with lacunar and cardioembolic strokes of moderate severity. Therapy with emoxipin increased endogenic antioxidant activity and improved a clinical status of the patients. The protective effect of carnosine was demonstrated in experimental acute hypobaric hypoxia and cerebral ischemia in rats. The results obtained permit to recommend an inclusion of both emoxipin and carnosine in a combined treatment of ischemic disorders of cerebral circulation.

Animals↗

PubMed2000

Functional interaction between various glutamate receptors.

The interaction of glutamate with various receptors in glutamatergic neurons and functional interaction between glutamate receptors are reviewed. It is hypothesized that metabotropic receptors perform defensive functions in the brain by protecting neurons from neurotoxic effects caused by excessive glutamate release.

Animals↗